Another new bone drug — Tymlos (abaloparatide) — recently hit the market, approved by the FDA for treating osteoporosis in postmenopausal women.

As always when we get a new entry into this ever-more-crowded market, I wanted to see how Tymlos works in the body and what downsides could be lurking behind all the hype. Is Tymlos safe? I wish I had a new and different message for you about Tymlos. Believe me, it would be nice to be able to say, for once, that the newest product on the bone drug market really is good for bones — and safe for those who take it. Unfortunately, I can’t say this.

Tymlos — how does it work?

Tymlos, like Forteo before it, works by imitating a natural bone-building process in the body to increase the patient’s bone density. It’s similar to Forteo in that it focuses on the parathyroid hormone (PTH) pathway, except that while Forteo mimics PTH itself, Tymlos mimics a peptide called human parathyroid hormone-related protein (PTHrP) — but the end result is the same: stimulation of the PTH pathway to increase osteoblast activity, with the goal of building denser bone. If Tymlos works along similar lines as Forteo, then it stands to reason that it’s going to have similar drawbacks — and it does.

The side effects of Tymlos — a deeper look

Like Forteo, Tymlos comes with a warning about osteosarcoma, a rare bone cancer. The warning is based on animal studies that have shown increased rates of this cancer in animals dosed with abaloparatide (Tymlos). Rather ironically, one study cheerfully noted that their results “suggest no increased risk of osteosarcoma would be expected in patients treated with [Tymlos]” in comparison to Forteo — which itself offers a greater-than-normal risk of osteosarcoma, so that’s not much of a recommendation.

Another adverse effect in the warning list is orthostatic hypotension — that is, low blood pressure upon standing, which could lead to fainting or falls (not something you want in a person at high risk of fracture!). High blood or urine calcium levels (the latter in association with kidney stones) are also concerning side effects.

Further, the effects of this drug on the immune system is really unexplored and only lightly touched upon in the safety trials. Half of the individuals using the new drug developed antibodies to the drug which in some cases lead to cross-reactivity, and in all cases squantered precious immune system focus and energy.

It’s also notable that a large, double-blind clinical trial with 2,463 women (age 49–86) comparing Tymlos directly to Forteo and placebo, Tymlos significantly outstripped both the placebo group and the Forteo group in terms of participants who had to stop treatment due to side effects such as nausea, dizziness, headache, and palpitations; where the Forteo group had about an 0.7% absolute increase in such side effects over the placebo group (a relative increase of 11%), the Tymlos group experienced a whopping 3.8% increase (a 61% relative increase) in these effects over the placebo group.

How much does Tymlos really reduce fracture?

I bring up the “absolute” vs. “relative” increases in side effects for a reason: The 43% nonvertebral fracture risk reduction in Tymlos-treated patients sounds fantastic until you realize it’s relative risk, not absolute risk. In absolute terms, the placebo group had 2% more nonvertebral fractures than the Tymlos group — meaning for every 100 women who took this drug and dealt with its side effects, 2 were spared a nonvertebral fracture who would’ve had one if they’d done nothing. And how about vertebral fractures? This new drug was only slight more successful at reducing vertebral fractures — reporting a absolute reduction of 3.64%. One hundred women have to be treated for 3.64 spinal fractures to be prevented. (Given the exorbitant cost of this drug, that’s not such a great return on investment!)

Ultimately, this drug has the same problems most of the others have — it hijacks the body’s natural processes to force a result without consideration for the unintended consequences. Which begs the question: Why not work with the body to strengthen bones the way nature intended?

Recently, Sarah came to my office reporting that her doctor wanted her to take the bone drug raloxifene (Evista™). She wanted to know if I thought this medication would benefit her, so I sat down to take a fresh look at the first and largest controlled study on this drug.

The short version of what I discovered: there is limited benefit and substantial risks with this bone drug. But to understand why, you need to know the long version: what this drug does, and what it doesn’t do.

What is raloxifene (Evista™)?

Raloxifene is a “selective estrogen receptor modulator (SERM),” which puts it in the same family as the breast cancer drug tamoxifen (it was studied for breast cancer, but proved less effective than tamoxifen). SERMs bind to estrogen receptors and mimic estrogen’s effects; the idea is that you can get estrogen’s beneficial impacts on bone, but without the negative estrogen effects of on the uterus endometrial and breast tissue.

What raloxifene’s fracture prevention trial reveals

Back in the late 1990s, researchers conducted the first (and largest) placebo-controlled fracture prevention trial to determine what raloxifene might offer for osteoporosis. This trial involved 6,828 postmenopausal women divided into two treatment groups: One that was given a placebo, and the other given raloxifene in either 60 or 120 mg daily doses.

All of the study subjects had osteoporosis as determined by bone density measurement (–2.5 T score), and some of the women had already experienced a spinal fracture. The study was three years in duration.

Fracture reduction at three years:

Of the 6,828 women in the study, 503 (7.4%) experienced at least one new vertebral fracture during the study period.

In the placebo group, 10.1% experienced a vertebral fracture visible on x-ray (not necessarily symptomatic) during on the 3-year study.

In the treatment group using 60-mg doses of raloxifene, 6.6% experienced a new vertebral fracture. This represents an absolute risk reduction of 3.5% — that is, among those using raloxifene, 3.5 fewer vertebral fractures occurred per 100 women as compared to those not taking the drug.

Importantly, there was no significant reduction in hip fracture or other non-vertebral fractures with the use of raloxifene. While spinal fractures are a key warning sign for osteoporosis, they don’t affect quality of life nearly as much as hip fractures do.

All in all, this very large study showed that this drug had a small effect on reducing vertebral fractures and no significant effect on reducing hip or other non-vertebral fractures.

The risks of raloxifine lead to FDA black box warning

Unfortunately, even this very first study on raloxifene reported serious adverse effects, most notably a three-fold increase in the risk of potentially life-threatening venous blood clots (thrombosis).

Ten years after the drug was approved, the FDA issued a black box warning about this side effect — which is the most serious notification of potentially life-threatening adverse effects the FDA can require, short of withdrawing the drug from the market. I’ve reproduced it here so you can see what it says.

Is there a better way?

After looking at this information and comparing the mild possible benefits to the significant potential harms, Sarah and I have to ask the question: Is there a better way?

Currently, there are number of bone drugs prescribed to intervene with the mechanisms of skeletal weakening, and many more are in the pipeline. Given that up to half of the women 50+ in this country will be told to take a bone drug at some point, it’s a great idea to take a look at what these drugs do, the degree to which they really prevent fracture, and their potential risks, and what other avenues might be available to you.

Then make up your own mind.

Here at the Center for BetterBones we know there is a better way and it is our mission and passion to share with you our time tested, fully life-supporting BetterBones, Better Body Program.

Our skeletons were meant to last a lifetime, so when they show signs of not living up to this promise, we need to stop and ask ourselves, “What’s causing bones to weaken?”

Seems only logical, right?

While this is how thoughtful osteoporosis treatment begins, having spoken with thousands of individuals diagnosed with osteoporosis, I can’t help but notice a glaring difference between how women and men are treated when a bone health concern arises.

The double standard of conventional osteoporosis treatment

As a rule, women are told to take bone drugs when their T scores get to -2.5 or greater — without any investigation into the possible causes of their bone weakening. Often, they’re not even carefully questioned about their history, or even given a simple test for vitamin D adequacy. For a man with similar bone density or fracture history, however, a medical workup is usually ordered; he’s not simply handed a bone drug script.

Let me illustrate these statements with the cases of Sally and Robert.

Sally, a 61-year-old woman, experienced a spinal compression fracture and was found to have low bone density. Her hip and spine T-scores were -2.5 and -2.7, so she was diagnosed with osteoporosis. The doctor felt Sally’s osteoporosis was potentially dangerous, so he recommended bone drugs, despite all their limitations and unwanted side effects, as treatment. His recommendation was accompanied by remarks like, “You’ll fracture if you don’t.” When Sally expressed doubts, she heard, “You’ll end up disabled.”

At the Center for Better Bones, we take the position that if the doctor thinks the problem is serious enough to warrant bone drug use, then it is surely serious enough to warrant a search for the causes of this problem. Yet Sally wasn’t given even one of the medical tests commonly used to identify causes of bone weakening. She was simply and forcefully told to take bone drugs.

Richard, a slender, 55 year-old man with T-scores of of -3 in the hip and -2.5 in the spine, had no fractures. Like Sally, Richard was diagnosed with osteoporosis and offered bone drugs — but beforehand, he was subjected to one of the most comprehensive osteoporosis workups I’ve ever seen. He was tested for vitamin D, parathyroid hormone, loss of calcium in the urine, blood calcium, bone formation markers, celiac disease, autoimmune factors, a hormone panel, comprehensive nutrition testing — even tests looking for unusual bone marrow disorders. The irony is, men in his family have a tendency to have low bone mass, yet none ever had a significant osteoporotic fracture — so he was given this battery of tests (and offered drugs) despite personal and familial history suggesting his fracture risk was low.

While these are just two cases, this is something I typically see in my clients: women are rarely given the same sort of medical workup for osteoporosis as men, even when (as in Sally’s case) they have already had an osteoporotic fracture.

Finding hidden causes of osteoporosis

Of course, we should all review and correct any shortcomings in diet, lifestyle, exercise, behavior, and even thought patterns that contribute to less-than-ideal bone health. But if you have excessive bone loss or low-trauma fracture, women especially should seek out a physician who will look forunderlying medical causes of bone weakness. As a guide, you might print out my list of osteoporosis workup medical tests to give your doctor. Follow this up by politely askingto be treated… like a man.

I’ve argued for years that bisphosphonates — the knee-jerk bone drugs recommended for those with osteoporosis regardless of their actual fracture risk — quite often offer no benefit to those who are prescribed them, and for many, do more harm than good. That’s why I was alarmed, but not surprised, by a recent study that found bisphosphonate drugs may be leaving bones weaker — not stronger — at the microscopic level (Ma et al, 2017).

In the study, researchers obtained samples of trabecular bone from three groups of subjects: (1) normal, healthy older adults who had no fractures, (2) individuals who had fractured a bone after at least 1 year of treatment with bisphosphonates, and (3) individuals who’d had fractures but were not being treated for osteoporosis.

They first examined the bones’ microstructure and identified areas of osteoclast activity (“perforations”) versus microscopic fractures (“microcracks”). Then they subjected each sample to load-controlled tensile testing to determine how much strain the bone could withstand.

The results were revealing. The first group (no fractures) had the least amount of either perforations or microcracks. Both the second (untreated with fractures) and third (bisphosphonate-treated with fractures) groups had roughly equivalent amounts of perforations and microcracks. But the big difference was the volume of perforations versus microcracks: the untreated group had a significantly higher volume of perforations while the bisphosphonate group showed a significantly higher volume of microcracks.

It’s pretty clear that the untreated patients who’d had fractures were undergoing high bone turnover — that’s why they had more (and larger) osteoclastic perforations. But bisphosphonates-treated group had significantly larger microcracks — which suggests that in the bisphosphonate group, either the bone is much less resilient and more prone to cracking under strain than normal bone, or the usual repair mechanisms aren’t working up to standard. Or both at the same time!

More to the point, it suggests that people treated with bisphosphonates have bones that are significantly weaker and more prone to fracture than either healthy people or people with high bone turnover.

The tensile strength testing performed on all three groups’ samples confirmed this: Where the normal group had a tensile strength (measured in megapascals) of 1.62 MPa, the untreated fracture group’s tensile strength was decreased by about 47% (to 0.86 MPa) — and the bisphosphonate group’s tensile strength was an astonishing 64% (0.58 MPa) below the normal group’s level.

This means that people treated with bisphosphonates have much weaker bones than even people at high risk of fracture due to high bone turnover!

If using bisphosphonates leaves patients with slightly denser but significantly weaker bones, increasing the likelihood of a catastrophic fracture (never mind the other side effects). So all this leaves us asking, “What exactly is their benefit?

When the American College of Physicians (ACP) recently updated its guidelines for treating osteoporosis (Qaseem et al, 2017), tucked in with the usual recommendations for drug therapy was something major: The ACP reversed its position on estrogen therapy for osteoporosis.

In 2008, ACP guidelines supported estrogen therapy based on “high-quality evidence that estrogen therapy was associated with reduced risk for … fractures in postmenopausal women.” In direct contrast to this, the new guidelines state that “[m]oderate-quality evidence showed no difference in reduced fracture with estrogen treatment in postmenopausal women with established osteoporosis.”

Why guidelines on estrogen therapy for osteoporosis have changed

How is it possible to have “high-quality evidence” that something works and a few years later, it somehow doesn’t? It’s all about how you look at the data. The 2008 guideline based its recommendation on studies showing estrogen decreased fracture risk—but, as the 2017 guideline points out, “many of these studies focused on postmenopausal women with low bone density, or on postmenopausal women in general rather than those with established osteoporosis.” In other words, the 2008 evidence came from women who did not have osteoporosis — the problem the guidelines are meant to address.

In the intervening years, a bunch of randomized clinical trials were done examining estrogen’s effects on women with osteoporosis to offer better information. Since estrogen offers little benefit and has known harms, like increased risk of stroke or breast cancer, the ACP’s decision to change their recommendation makes perfect sense. It also highlights two important points when it comes to science — one, it’s always changing with new information, and two, a lot depends on the assumptions of the people looking at the evidence.

It’s enlightening to look at the ACP osteoporosis guidelines side-by-side with the 2013 European Union osteoporosis guidelines (Kanis et al., 2013). The European recommendations start by discussing mobility, falls, and diet and nutrition before weighing the pros and cons of bone drugs. The ACP guideline starts with drug therapy and mentions nutrition only in passing (the usual suspects, calcium and vitamin D, nothing more) and devotes only three lines to exercise.

The ACP’s guideline assumes that drug therapy is the best approach. The Europeans look at it differently — and so do I. My Better Bones, Better Body approach has stayed pretty consistent over the years because it’s based on the understanding that the body knows how to heal itself if it has the resources it needs!

When the bone drug Prolia (denosumab) first came out in 2010, I took a hard look at it because it used a completely different mechanism than widely used bisphosphonate drugs, focusing on the RANK/RANK-L/OPG system to prevent osteoclasts from being “activated” instead of decreasing their number like bisphosphonates. I wasn’t satisfied in 2010 that this drug was any safer or more effective than bisphosphonates, and sad to say my skepticism has been borne out by recent research.

Is a Prolia a blockbuster bone drug — or a bust?

The FREEDOM Trial, which studied Prolia use in postmenopausal women for 3 years, found very little reduction in fracture risk. Vertebral and hip fractures were reduced 4.8% and 0.3% — meaning for 100 women they treated, only 5 saw fewer vertebral fractures than you’d expect with a placebo, and not even one woman was spared from a hip fracture by the drug. Given that hip fractures are considerably more harmful than vertebral fractures, these are minimal benefits indeed.

Although gains in bone density were observed, those gains were lost within 1 year of halting the drug (Cummings et al., 2017).

Furthermore, once they stopped using Prolia, patients’ risk of vertebral fracture quickly (<1–2 years) reverted to the same risk seen in those who’d never taken the drug in the first place (Cummings et al., 2017). They also lost a significant amount of the bone they’d gained by using Prolia—35.5% of the total gain in the spine, 44.6% of the total gain in the femoral neck, and 103.3% in the total hip (Zanchetta et al., 2017). In other words, the drug offered no lasting benefit.

Much more concerning: the finding that patients were more susceptible to having multiple vertebral fractures after discontinuing Prolia than patients who’d never taken the drug at all — and it was especially high in those who’d had such fractures prior to going on the drug in the first place (Cummings et al., 2017; Anastasilakis et al., 2017). This finding confirmed a number of earlier case reports of “rebound fractures” in patients who had discontinued Prolia within the preceding 12 months. Researchers speculated such fractures were a consequence of sudden renewal of bone resorption after the drug was stopped in combination with the absence of repair mechanisms during its use (Anastasilakis et al., 2017; Lamy et al., 2017; Polyzos & Terpos, 2016).

I’ve said repeatedly that working against nature invites unintended consequences, so I’m not surprised by these results. What is disappointing is the continued emphasis on the “magic bullet” approach to osteoporosis, when it has been clear for so many years that it just doesn’t work.

It’s no secret that I’m no fan of bone drugs in general. I’ve found the arguments for their use deeply unconvincing for decades. And now, European researchers looking at the accumulated evidence about the various drugs’ long-term effects are starting to come to the same conclusion:

Except in extreme cases, bone drugs don’t offer enough benefit in reducing the risk of fractures to be worth the price paid in terms of both short- and long-term side effects.

A European/Canadian research group reviewed the evidence on bisphosphonates like:

alendronate (Fosamax),

ibandronate (Boniva) and zoledronic acid (Zometa or Reclast)

teriparatide (Forteo)

denosumab (Prolia)

two treatments not used in the U.S.: calcitonins and strontium ranelate

Their findings struck me as good general “lessons” for all of us to learn.

‘Denser’ bones are not always stronger bones

The review found that the majority of osteoporotic fractures happened in those who did not have “osteoporotic bone density.” This helps confirm: Bone density alone cannot predict fracture risk.

Other recent studies show a large percentage of people who fracture have only osteopenia or even normal bone density. Many people with an osteoporotic bone density never fracture.

Not all fractures are created equal

When it comes to assessing bone drugs’ effects, a painless vertebral fracture or a toe fracture (painful, but not life-altering) shouldn’t be considered as clinically important as a hip fracture, which is life-changing.

Yet many drug trials either focus on vertebral fractures or on “non-vertebral” fractures as an endpoint. The stubbed toe becomes equivalent to a hip fracture in determining how effective the drugs are in fracture prevention.

Not surprisingly, when hip fractures are looked at specifically as the endpoint of choice, the researchers discover something different. They found that the data on less serious fractures of toes, wrists and so forth obscure the fact that the drugs don’t do much to prevent the most serious and dangerous osteoporotic fractures.

Bone drugs’ benefits remain inconclusive

The benefits of taking a bone drug must outweigh the costs for it to be worth recommending. And even in high-risk older adults, such benefits have not been shown conclusively.

In weighing the risk-benefits of bone drugs, researchers took a hard line on the importance of evaluating all costs. “Clinical trials evaluating harm-benefit balance in osteoporosis or fracture prevention should be well-powered long-term studies that include hard endpoints,” they note. “Total mortality, total serious adverse events, hip fractures, and functional status are essential outcomes.”

New U.S. osteoporosis guidelines miss the mark

What’s frustrating to me is that experts in the U.S. still focus uncritically on the flawed studies that the review critiques. They glibly parrot the ideas that bone density is the same thing as fracture risk and that drugs offer protection from fractures.

Case in point: The American College of Physicians’ latest osteoporosis guidelines, which were published virtually simultaneously with the European review. They make a “strong recommendation” for the use of bisphosphonate drugs “to reduce the risk of hip and vertebral fractures.” Most galling to me, they openly equate bone mineral density with fracture risk: “most women with normal DXA scores” it notes, “do not progress to osteoporosis within 15 years.”

To which I respond with the European review’s first lesson: Denser bones ≠ stronger bones.

Quite frequently women write me to ask: What is strontium and why do you include it in your Better Bones Builder?

Well, there’s a short answer and a long answer to that question. Here’s the short answer: Strontium is an element very much like calcium and naturally present in our food and water. If you are eating a typical diet, you might getting anywhere from 1 mg to more than 10 mg of strontium per day. The reason it’s in the Better Bones Builder is that the elemental form (that is to say, the non-radioactive version found in nature) has been shown to promote formation of healthy teeth and bones. So it makes sense to include dietary doses of strontium in comprehensive bone-building formulas such as our Better Bones Builder because low-dose strontium is a companion nutrient that works with calcium and other minerals to promote bone health.

Low-dose vs. high-dose strontium

Now let’s get to the long answer. Where confusion sets in is when people hear about strontium being used by itself to build bone. What most people don’t realize when they read about strontium as “the solution” for bone health is that such talk isn’t referring to dietary doses of elemental strontium — rather, it’s referring to the extremely high-dose strontium that has been developed and patented as a drug therapy for osteoporosis in Europe. This drug, known as Protelos®, contains 680 mg of elemental strontium and two grams of strontium ranelate, a synthetic salt that combines strontium with ranelic acid.

Risks of high-dose strontium

Elemental strontium is different

Elemental strontium is a natural part of the earth’s crust and is very different from “strontium 90” which is a hazardous radioactive nuclear fallout product from aboveground nuclear testing. All strontium used in bone-building health products is elemental strontium.

One goal of Protelos® is for a small number of strontium atoms to displace calcium atoms in bone. For this effect it is necessary that the strontium drug be taken at least two hours apart from calcium. This separation of calcium from strontium is not necessary for low-dose strontium (22 mg) like that in my bone-building formula, which is used as a nutrient to aid the development of healthy bones. Unlike dietary strontium, the strontium drug has been found to have various adverse side effects including nausea, diarrhea, and, more rarely, memory problems, serious skin rashes, and venous clots. For the first 10 years of its use as an osteoporosis drug, however, more serious drug-induced problems were detected as the strontium drug (Protelos®) was found to substantially increase the risk of heart problems, including heart attack. In 2014, the European Medicines Agency Pharmacovigilance Risk Assessment Committee (PRAC) concluded that the risks of the strontium drug outweighed the benefits and they recommended suspension of its use.

Specifically, PRAC reported in 2014 that:

For every 1,000 patient years of use of the strontium drug (Protelos®) there were 4 more cases of serious heart problems and 4 more cases of blood clots or blockages of blood vessels than there were with the placebo.

As for benefits, the strontium drug had only a modest effect in osteoporosis, preventing 5 non-spinal fractures, 15 new spinal fractures, and 0.4 hip fractures for every 1,000 patient years.

Later in 2014 this same European committee revised its recommendation allowing the strontium drug to be used by patients who could not be treated for osteoporosis by other bone medicines, but requiring that patients using the strontium drug be carefully monitored. In addition, those with a history of heart or circulatory problems were not allowed to use this medication.

The high-dose strontium drug is not available in the U.S.

Keeping strontium in perspective

To avoid any confusion, let me be perfectly clear: In the U.S. the strontium drug Protelos® is not approved for use as a bone drug, and it is not available here for purchase. In the U.S. and Canada, however, one can purchase equally high dose natural forms of strontium as strontium citrate or strontium carbonate and some companies promote bone support formulas with 680 mg elemental strontium (the same strontium dose as in the Protelos® strontium drug formula). Keep in mind that this high-dose strontium, be it natural strontium as sold in the U.S. or synthetic as in Protelos®, is best viewed as a “bone drug,” and, as with all bone drugs, it should be used with great caution. While the synthetic strontium drug (Protelos®) has been shown to carry serious adverse effects, to date there have been no studies on the safety or efficacy of high-dose (680 mg) natural strontium as sold here in the U.S.

Here at the Center for Better Bones our mission is to explore the full human potential for natural, life-long bone health. We strive to work with nature and in accord with nature when at all possible. The Better Bones, Better Body program includes small low doses of supplemental strontium, while not generally recommending the use of high-dose strontium (680 mg) or conventional bone drugs.

I hope this helps clear up the confusion when it comes to strontium. I will be writing more on strontium in the future, so stay tuned!

Are your medications dangerous to your bone health? While we all know that medications have some side effects, we may not recognize that certain medications, especially used long term, can seriously harm your bones.

Let’s look at the 3 most commonly used classes of medications known to increase fracture risk.

Which medications damage bone?

Corticosteroids. This class of drugs interferes with bone formation while simultaneously stimulating bone resorption, thus accelerating bone loss significantly. At one point, scientists estimated that approximately 20% of all osteoporosis in the U.S. was the result of corticosteroid use, and it is estimated that up to 50% of patients using long-term oral corticosteroids will develop bone fractures.

While short-term, very occasional steroid use has less potential to weaken bone, longer-term use of oral and even inhaled steroids clearly jeopardize bone strength and increase fracture risk. Doses as low as 5 mg a day have been shown to increase fracture risk.

It is wise to seek alternatives to steroid therapy, use them when only truly necessary and for the shortest period of time possible, and to fully support your bone health while using them to help offset the drug’s effects.

Common corticosteroids

Beclomethasone (inhaled)

Betamethasone (lotion or cream for skin)

Budesonide (oral capsule, inhaler and nasal spray)

Ciclesonide (inhaled)

Cortisone (oral, injection)

Dexamethasone (oral)

Ethamethasoneb (oral, injection)

Flunisolide (inhaled)

Fluticasone (inhaled)

Hydrocortisone (spray, liquid, lotion, gel, cream, ointment)

Methylprednisolone (oral)

Mometasone (inhaled)

Prednisolone (oral)

Prednisone (oral)

Triamcinolone (oral, injection

Antacids

Antacids. Proton pump inhibitors such as esomeprazole (Nexium) and lansoprazole (Prevacid) are commonly used antacids. These antacid drugs powerfully reduce the production of stomach hydrochloric acid and thus likely weakened nutrient absorption. Proton pump inhibitors have been repeatedly documented to increase the risk of hip, wrist, and spine fractures.

H2 receptor antagonist drugs like cimetidine (Tagamet) and ranitidine (Zantac) are also used to suppress acid production, which suggests that they might impair nutrient absorption similarly. However, studies have suggested that they do not seem to increase fracture risk as do proton pump inhibitors. One reason may be that they work by blocking the action of histamine — a chemical released in immune responses. Histamine tends to promote bone resorption. So these drugs are less likely, long term, to promote bone loss. Even so, there are studies showing that bone loss occurs in people taking H2 receptor antagonists if they do not have good intake of specific key bone nutrients, such as calcium and vitamin D.

Antidepressants

Antidepressants. A specific class of antidepressant medications called selective serotonin reuptake inhibitors (SSRIs) is associated with a significant increase in fracture risk. One study noted that there are some indicators that the medications have direct effects on bone, but they’re not well determined. However, the impact of SSRIs on balance and alertness are well established.

What it boils down to is this: if you take SSRIs, it’s important to look carefully at your bone health. Even in the absence of a direct effect on bones, falling is the primary cause of fracture in those with weakened bones.

Take action!

I realize that it’s not always possible to avoid these medications, but there often exist dietary and lifestyle changes and alternative medical approaches that go to the root of the disorder and reduce the need for bone-damaging medications. Also, once you know your medication may harm your bones, you can take steps to protect your skeleton. Plus, by knowing what the medications are, you can talk with your practitioner to determine whether there are less bone-damaging alternatives and support your body’s natural healing processes as much as possible.

The next big new bone drug is about to hit your doctor’s office. Impressive claims that the drug reduces fractures by 73% are being tossed around. But bisphosphonates were once touted in similar terms and are falling out of favor due to side effects and limited efficacy.

Do the stats in these studies mean anything real?

Whenever I hear about a new bone drug, I look at the research and ask a set of key questions to see whether there is any good news. I’m sharing them with you so you have tools to help you assess what you hear.

Question #1: What’s the nature and action of the drug? What will its long-term effects be?

The experimental bone drug I mentioned is a monoclonal antibody called romosozumab that inhibits action of a protein in the body known as sclerostin. Some time ago, it was discovered that sclerostin deficiency causes a rare genetic disorder characterized by high bone mass and resistance to fracture, so the pharmaceutical industry decided to make a drug to block this protein and see if it could reduce bone breakdown and enhance bone buildup.

Now Romosozumab is a drug that tinkers with both bone breakdown and bone formation in a whole new way, and its discoverers claim that “the risk of new vertebral fracture was 73% lower in those who took the drug.” Pretty impressive, if it’s true. So let’s take a closer look and continue asking questions.

To begin with, an important unanswered question is, “What are the many roles that sclerostin plays in the body, and what will be the long-term impact of suppressing this protein?” The current study does not address the issue of long-term impact or safety, and it often takes 10+ years to see the full effects of such tinkering with human physiology. For now, we know roughly how the drug acts, but we do not know what its long-term effects are.

Question #2: How many people participated in the study, and how were they selected?

This study looked at 7180 postmenopausal women ages 55 to 90 with a hip bone density T score between -2.5 and -3.5. The group was divided into two subgroups — 3325 who took the drug, 3327 who were given a placebo. So on the surface, this is a strong study — it includes a large sample of individuals who are similar in age, gender, and baseline bone density, and the groups are equivalent in size.

But a closer look shows that those at higher risk of fracture were excluded from the study. That includes women with a hip T score worse than -3.5, a history of hip fracture, or even one severe or more than two moderate vertebral fractures; those with a vitamin D below 20 ng; women with high or low blood or calcium as well as those with bone diseases or conditions affecting bone metabolism.

In other words, they chose participants based on low bone density rather than fracture risk (and if you’ve read my blogs, you know that the two aren’t necessarily the same).

Question #3: How long was the study?

Study subjects were only given the new drug, romosozumab, for 12 months and then switched to another monoclonal antibody bone drug, denosumab (Prolia®), in the second year. While researchers do not explain why they switched to another drug, I suspect they feared extended use of this new drug would result in serious longer-term adverse effects. This is not unlike the case with the drug teriparatide (Forteo®), the use of which is limited to two years due to potential life-threatening impacts.

Question #4: What is the real-life fracture-reduction benefit?

The length of the study is important because the short-term fracture reduction benefits may be very different from the long-term ones. In this case, all we have is a 1-year study with romosozumab and then another year-long study switching all study subjects (those on placebo and those on romosozumab) to the denosumab (Prolia®) bone drug. This makes the study a little confusing, but I’ll try to clarify the findings:

Only a few vertebral fractures were prevented by using either of the two drugs. The study had a total of 6,652 women, all of whom had a pretty low fracture risk to begin with. In the first year of the study using romosozumab versus placebo more than twice as many women (59) in the placebo group experienced vertebral fractures than the women in the romosozumab group (16). So when you look at how many women were spared from a vertebral fracture by taking the new drug (that is, 59 – 16 = 43 women), you realize that for every 1 woman who benefited, there were 76 others in the drug group who took the medication and got nothing out of it. If your doctor told you he had to treat 3,327 women to prevent just 43 vertebral fractures, you might look into other ways to strengthen your spine.

Both drugs put together had very little benefit on vertebral fracture. Among the 3,327 women who received placebo the first year and then were put on denosumab in the second year, there were 84 new vertebral fractures, whereas the women who took romosozumab the first year had only 21. Overall, then, 63 women out of 6652 were saved from having a fracture by taking bone drugs for both years. That’s not even 1% of the total number of participants.

The new drug had almost no impact on non-vertebral fractures. Vertebral fractures often cause no symptoms in those who have them, but others — like fractures in the wrist, collar, arm or hip — can be more serious and painful. Such fractures occurred in 56 patients on the new drug and 75 in the placebo group. That means the drug helped prevent only 19 of the 3,327 women avoid non-vertebral fractures with over 1 year of treatment. So you’d have to treat 175 women to save just 1 woman from fracturing a hip. And when you take the second year into account, when all the participants took bone drugs, you find no significant difference in risk between the romosozumab group and the placebo group. So if you were looking to prevent fractures of the hip, wrist, collarbone, arm, or other non-vertebral fracture, the new drug was no help at all.

Question #5: What are the reported and potential adverse effects of the drugs?

In this 1-year trial of romosozumab, adverse effects included the following: hypersensitivity to the injection; 2 cases of osteonecrosis of the jaw; 1 atypical femur fracture; a high incidence of anti-romosozumab antibodies (the impact of this on the immune system is yet unknown); and lowered serum calcium levels in those using romosozumab. These are all fairly serious problems.

Is there a better way to reduce needless fractures?

From my nearly 3 decades of clinical practice and bone health research, I confidently say yes, there is a better way! And that better way is one that builds Better Bones and a Better Body naturally, without the many risks of bone drugs.

Approaches like my Better Bones Program enhance health, vitality, and fitness while reducing fracture risk. Why not take a few minutes to review the steps to the Better Bones, Better Body Program and get started strengthening your bones today?